Although agency staff had questioned the product's efficacy and safety in briefing documents prepared for the Wednesday meeting, most committee members said they were satisfied that the new formulation would work as well and as safely as an existing nebulized liquid tobramycin product.

The FDA usually follows its advisory panel recommendations but is not required to do so.

Both tobramycin products are made by Novartis. The company told the FDA's Anti-Infectives Advisory Committee that the dry-powder version would make the drug easier for patients to use and could therefore improve treatment adherence -- a common problem for cystic fibrosis patients, who must spend hours each day preparing and administering a variety of medications.

The currently approved nebulized product, sold under the brand name TOBI, itself requires about 30 minutes for each twice-daily dose.

Novartis hopes most patients can transition to the dry-powder form, which comes in a prepackaged capsule that patients insert into an inhaler device similar to others on the market for asthma medications. The company estimates that patients would need only 5 minutes to dose themselves with the required four capsules, to be taken twice daily.

As with TOBI, the dry-powder form would be taken in cycles of 4-weeks-on, 4-weeks-off. This schedule was designed in an effort to minimize development of antibiotic-resistant strains of P. aeruginosa and/or other organisms.

In the briefing documents, FDA staff reviewers pointed to data from Novartis' studies indicating that resistance appeared to develop anyway with the new formulation, in the form of increased minimum inhibitory concentrations over time.

They also expressed concerns, repeated during an oral presentation at the Wednesday meeting, that patients may spread these resistant organisms to other people in close contact.

Another negative for the product was a relatively high incidence of coughing.

However, panel members largely dismissed those concerns as theoretical. They were persuaded by the primary outcome data showing that the new formulation was superior to placebo and similar in efficacy and safety to the nebulized form.

Said committee chairman Thomas A. Moore, MD, of the University of Kansas in Wichita, "I think safety and efficacy were proven by the sponsor today."

Michael Neely, MD, of the University of Southern California in Los Angeles, who also voted to support approval, agreed with the FDA staff review that trial data contained some holes.

Diane Cappelletty, PharmD, of the University of Toledo, recommended that, if the product is approved, postmarketing studies should take a closer look at its adverse effects, including more serious outcomes such as death and dyspnea as well as the incidence and severity of coughing.

One issue that panel members spent substantial time discussing was the inhaler device's ease of use. A study submitted by Novartis indicated that five steps in working the device that the company deemed "critical" were successfully completed by nearly all patients.

But several steps considered noncritical had lower success rates. Fewer than half of patients positioned the device according to instructions when piercing the capsules.

An FDA analysis that included following instructions to inhale twice from each capsule and to check it afterward to confirm that the drug had been inhaled -- considered noncritical by Novartis -- showed an overall success rate of just 53%.

Most panel members, though, indicated that they weren't very concerned about patients' ability to manage the device.

"It doesn't strike me as any harder than any of the other things" that cystic fibrosis patients use daily, said Cappelletty.

The lone dissenter on the panel was consumer representative Rodney Mullins, of Public Health Consultants and Advocates in Duluth, Ga.

In explaining his "no" vote, he said the data on adverse effects and the emergence of potential drug resistance were too scant to warrant the product's approval.

"I think we do a disservice to the CF population with this incomplete data," he said, arguing that the committee was unable to "assure the American public that this product is safe."

Neely, however, said, "We can't prevent every adverse event. I didn't see a signal that we would be harming anyone" if the product was approved.

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